Gurudutt Pendyala, PhD, Robert Lieberman Professor in the UNMC Department of Anesthesiology, received a two-year grant from the National Institutes of Health to study the mechanisms underlying prescription opioid use post social defeat (bullying) in HIV-positive (HIV+) adolescents.
From a developmental milestone, adolescence is a critical phase with changes occurring on different tiers — physical, cognitive, emotional, social and behavioral. Dr. Pendyala said the risk of contracting HIV increases at this time. There also is a high risk of passing the virus to others when left untreated or if adolescents do not know they are infected.
Due to the social stigma in some communities, being HIV+ leads to high rates of depression, anxiety, low self-esteem and less adherence to medications, impacting behavior and increased drug dependency and abuse in these individuals.
“Any negative experiences during this critical developmental period can significantly impact the outcomes, with serious ramifications that could persist into adulthood,” Dr. Pendyala said. “This problem is further aggravated in HIV+ adolescents due to the associated stigma, negative attitudes and prejudice in society.”
Dr. Pendyala said previous studies had found a correlation between social stress and increased stress-related psychiatric and addictive disorders, but molecular mechanisms contributing to these outcomes remain unclear.
These molecular mechanisms will be explored in the study using adolescent rats expressing key genes of the HIV genome – an advantage because of the high amount of genome overlap with human adolescents, which mimics the pathophysiology in many diseases. Dr. Pendyala said the study would shed some light on the impact of social defeat, or bullying, during adolescence and the corresponding risk of becoming dependent on opioids.
“The two key aspects to this study are to compare how bullying impacts behavioral outcomes in the rats during adolescence and to identify novel plasma and brain-specific biomarkers which will be key for future testing in clinical trials in humans,” he said.
“Preliminary studies have shown alterations in brain-derived extracellular vesicles (BDEV) sizes with HIV infection,” Dr. Pendyala said. “Based on this premise, our hypothesis is that social defeat further exacerbates BDEV dynamics that aggravate synaptic injury and precipitates prescription opioid use.”
Dr. Pendyala said the results would fuel future studies and eventually help develop strategies to treat and improve neurological outcomes in this vulnerable population.